Overview
UMMARY Background: The storage of vitamin A and the structural effect of hypervitaminosis A on the liver demonstrate implausible spatial and temporal patterns. Even though hepatic stellate cells are uniformly distributed within the hepatic lobules, there exists a genetically predetermined zonal gradient in the pattern of storage of vitamin A in the liver. Moreover, persistent hypervitaminosis A has been known to cause hepatic stellate cells hyperplasia and liver fibrosis. The temporal sequence and the possible spontaneous reversion remain largely unexplored. Objective: To determine the structural changes induced by persistent hypervitaminosis A in the liver and the short-term sequelae after its withdrawal A Study design: Quasi experimental study design Study setting: Departments of Human Anatomy, Human Pathology and Veterinary Anatomy and Physiology Materials and methods: Ethical approval to conduct the study was obtained from the Biosafety, Animal Use and Ethics Committee, Faculty of Veterinary Medicine, University of Nairobi. A total of 45 adult albino rats were used in this study and divided into 3 groups: A, B, and C. Group A rats were given 300,000 IU/Kg of vitamin A every alternate day via subcutaneous injection for 4 weeks with half of them being followed for a further 4 weeks off treatment. Group B rats were similarly given 300,000 IU/Kg of vitamin A every alternate day via subcutaneous injection for 8 weeks. Half of the members of this group were also followed up for 4 more weeks off treatment. Group C were the control group. All rats were maintained on a normal diet and fed ad libitum. Two rats from the control group were used for baseline results. Five rats from group A were euthanized at weeks 2, 4, 6 and 8 while those from group B were euthanized at weeks 6, 8, 10 and 12. The volume of rat xii livers were estimated using the Scherle method and SUR sampling used to select harvested liver segments. These were processed for histological staining using the hematoxylin and eosin, Masson’s trichrome and the periodic acid Schiff stains and images taken using a digital camera. General changes in the hepatic parenchyma were noted and recorded. Stereological methods were used to estimate HSC and hepatocyte area densities. Obtained data was keyed into the SPSS for coding, tabulation and statistical analysis. Means and standard deviations were then determined. The one-way ANOVA was used to compare the hepatocyte and HSC densities for the 3 groups and changes in densities over time. The Tukey test was used as the post-hoc test to detect between which groups the significant difference lay. A p value <0.05 was considered significant at 95% confidence interval. Results were presented in micrographs, tables and graphs. Results: There was a slight increase in the absolute liver volume with exposure to high dose vitamin A which continued to rise with stopping the exposure. The body mass normalized liver volume on the other hand, showed a marked reversible decline following persistent exposure to high dose vitamin A (p=0.074). Hepatic parenchyma distortion and hepatocyte and stellate cell vacuolation were more pronounced around the pericentral areas whereas the compensatory hyperplasia and hypertrophy of these cells seemed to emanate from the periportal areas. For both the acutely and persistently exposed groups, there was a significant temporal increase in hepatocyte density with exposure to vitamin A (p<0.001) followed by a significant decline when the exposure was stopped (p<0.001). Similarly, there was an increase in stellate cell densities (p=0.066) followed by a significant decline with discontinuation of exposure to vitamin A (p=0.013). Conclusion: Hypervitaminosis A causes significant but reversible spatial and temporal changes in both the gross and histological aspects of the liver. Withdrawal of exposure to vitamin A in cases xiii of suspected toxicity would therefore be paramount in the management of both acute and chronic hypervitaminosis A.
Sponser
Munguti, Jeremiah K.
Principal Investigator
Abstract
SUMMARY Background: The storage of vitamin A and the structural effect of hypervitaminosis A on the liver demonstrate implausible spatial and temporal patterns. Even though hepatic stellate cells are uniformly distributed within the hepatic lobules, there exists a genetically predetermined zonal gradient in the pattern of storage of vitamin A in the liver. Moreover, persistent hypervitaminosis A has been known to cause hepatic stellate cells hyperplasia and liver fibrosis. The temporal sequence and the possible spontaneous reversion remain largely unexplored. Objective: To determine the structural changes induced by persistent hypervitaminosis A in the liver and the short-term sequelae after its withdrawal A Study design: Quasi experimental study design Study setting: Departments of Human Anatomy, Human Pathology and Veterinary Anatomy and Physiology Materials and methods: Ethical approval to conduct the study was obtained from the Biosafety, Animal Use and Ethics Committee, Faculty of Veterinary Medicine, University of Nairobi. A total of 45 adult albino rats were used in this study and divided into 3 groups: A, B, and C. Group A rats were given 300,000 IU/Kg of vitamin A every alternate day via subcutaneous injection for 4 weeks with half of them being followed for a further 4 weeks off treatment. Group B rats were similarly given 300,000 IU/Kg of vitamin A every alternate day via subcutaneous injection for 8 weeks. Half of the members of this group were also followed up for 4 more weeks off treatment. Group C were the control group. All rats were maintained on a normal diet and fed ad libitum. Two rats from the control group were used for baseline results. Five rats from group A were euthanized at weeks 2, 4, 6 and 8 while those from group B were euthanized at weeks 6, 8, 10 and 12. The volume of rat xii livers were estimated using the Scherle method and SUR sampling used to select harvested liver segments. These were processed for histological staining using the hematoxylin and eosin, Masson’s trichrome and the periodic acid Schiff stains and images taken using a digital camera. General changes in the hepatic parenchyma were noted and recorded. Stereological methods were used to estimate HSC and hepatocyte area densities. Obtained data was keyed into the SPSS for coding, tabulation and statistical analysis. Means and standard deviations were then determined. The one-way ANOVA was used to compare the hepatocyte and HSC densities for the 3 groups and changes in densities over time. The Tukey test was used as the post-hoc test to detect between which groups the significant difference lay. A p value <0.05 was considered significant at 95% confidence interval. Results were presented in micrographs, tables and graphs. Results: There was a slight increase in the absolute liver volume with exposure to high dose vitamin A which continued to rise with stopping the exposure. The body mass normalized liver volume on the other hand, showed a marked reversible decline following persistent exposure to high dose vitamin A (p=0.074). Hepatic parenchyma distortion and hepatocyte and stellate cell vacuolation were more pronounced around the pericentral areas whereas the compensatory hyperplasia and hypertrophy of these cells seemed to emanate from the periportal areas. For both the acutely and persistently exposed groups, there was a significant temporal increase in hepatocyte density with exposure to vitamin A (p<0.001) followed by a significant decline when the exposure was stopped (p<0.001). Similarly, there was an increase in stellate cell densities (p=0.066) followed by a significant decline with discontinuation of exposure to vitamin A (p=0.013). Conclusion: Hypervitaminosis A causes significant but reversible spatial and temporal changes in both the gross and histological aspects of the liver. Withdrawal of exposure to vitamin A in cases xiii of suspected toxicity would therefore be paramount in the management of both acute and chronic hypervitaminosis A.
